Endogenous receptor identified for the spirit molecule
N,N-dimethyltryptamine (DMT) is not only the most potent hallucinogen known, it is also the only hallucinogen naturally produced in the human brain. DMT’s penchant for mind-altering dissociative states have led some to refer to the drug as the ‘spirit molecule.’ Users report sensations of extradimensional travel and vivid multimodal interactions with otherworldly intelligent beings. Some examples:
“I felt like I was in an alien laboratory, in a hospital bed like this. . . . A sort of landing bay, or recovery area. There were beings. . . .”
“They activated a sexual circuit, and I was flushed with an amazing orgasmic energy. A goofy chart popped up like an X-ray in a cartoon, and a yellow illumination indicated that the corresponding system, or series of systems, were fine. They were checking my instruments, testing things. When I was coming out, I couldn’t help but think `aliens.’ ”
“Dismemberment is part of the shamanic initiation, isn’t it? I felt a dragonlike presence. And, there were the same colors— red, golden yellows… The colors can be like a drape or a prelude or a curtain. Even
though they’re so pretty, you can get through them to the other side…“It was wild. There were no colors. There was the usual sound: pleasant, a roar, a sort of an internal hum. Then there were three beings, three physical forms. There were rays coming out of their bodies and then back to their bodies. They were reptilian and humanoid, trying to make me understand, not with words, but with gestures. They wanted me to look into their bodies. I saw inside them and understood reproduction, what it’s like before birth, the passage into the body. Once I established what they were communicating, they didn’t just fade away. They stayed there for quite a while. Their presence was very solid.” (Strassman 2000)
“They had a space ready for me. They weren’t as surprised as I was. It was incredibly un-psychedelic. I was able to pay attention to detail. There was one main creature, and he seemed to be behind it all, overseeing everything. The others were orderlies, or dis-orderlies.”
The sole endogenous source of DMT is the pineal gland, which is the pea-sized deep brain structure which Descartes hypothesized was the seat of the soul – the supernatural interface between the mind and the body. Scientists have hypothesized that DMT production in the brain could underlie natural psychedelic states like dream-sleep, psychosis, and mystical experiences.
Now scientists have identified the endogenous receptor for DMT: the sigma-1 receptor. First identified by pharmacologists in 1976, sigma-1 was originally believed to be an opioid receptor (The mu opioid receptor, for example, is the primary site of action for morphine; enkephalin and beta-endorphin have recently been identified as the endogenous [meaning naturally produced in the body] ligands for the mu receptor). However, the receptor was not affected by opiates or the opioid blockers naloxone and naltrexone, so it became a so-called ‘orphan receptor’. The sigma-1 receptor has unique properties: it does not closely resemble to any other known mammalian receptor, but it does share 30% identity and 66% homology with the fungal protein sterol isomerase; the receptor has no apparent role in cholesterol biochemistry like its fungal counterpart.
Reporting in Science this year, Fontanilla et al. show that DMT binds and activates the sigma-1 receptor in vitro and in vivo (2009). Furthermore, DMT binding to sigma-1 inhibits voltage-gated sodium channels in cardiac myocytes and neurons, and this inhibition is reversed by the antipsychotic haloperidol. Lastly, knock-out mice lacking sigma-1 show no behavioral change (vs. hyperactivity in controls) when administered DMT.
The authors conclude that the effect of DMT in the brain could be mediated by binding to sigma-1 receptors. That haloperidol (a first-line treatment for acute psychosis) blocks the effects of DMT at sigma-1 further supports the possible role of DMT in psychedelic states. The interaction between DMT and sigma-1 warrants further investigation as an intervention site and pathophysiological mechanism in neuropsychiatric disorders.
Sources
Strassman R (2000) DMT: The Spirit Molecule.
Fontanilla et al. (2009) “The hallucinogen N,N-Dimethyltryptamine (DMT) is an endogenous sigma-1 receptor regulator” Science 323:934-937.
Sigma-1 receptor. Wikipedia.
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